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Chronic Granulomatous Disease (CGD)Phase 1/2NCT07113743

Part B- G1X-CGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease

A Phase 1/2 study testing Busulfan, Tocilizumab and Eltrombopag in people with Chronic Granulomatous Disease (CGD), run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

Background: X-Linked Chronic Granulomatous Disease (X-CGD) is caused by a gene mutation that makes the immune system to not work properly. Researchers want to see if a lentiviral gene transfer treatment will have the ability to make the patient s immune system more normal, in particular reduce the risk of CGD related… Read more about this study

Who is it for?
Ages 3 to 60 years
Conditions the study is for
Chronic Granulomatous Disease (CGD)
What is being tested?
Busulfan, Tocilizumab and Eltrombopag
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
10 Sep 2025to 1 Sep 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • -Must have confirmed molecular diagnosis of X-linked CGD confirmed by deoxyribonucleic acid (DNA) sequencing and supported by laboratory evidence for absent or reduction >90% of the biochemical activity of the NADPH-oxidase.
  • At least 1 prior ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite conventional therapy.
  • No 10/10 HLA-matched donor available after initial search of National Marrow Donor Program (NMDP) registries within the last year.
  • Must weigh at least 15 kg.
  • Male or female, and must be at least 3 years of age but no older than 60.
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  • Parent/guardian must be willing to sign and date informed consent form for child and where appropriate, child may sign assent.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Ability to take oral medication and be willing to adhere to the prophylactic regimen.
  • Apheresis of patients for the hematopoietic stem cells collected as a part of this protocol will be performed according to the Standard of Care apheresis practices established in the NIH CC Department of Transfusion Medicine or at their local facility. If performed at
  • their local institution, the patient will have consented onto the gene therapy study prior to collection; however, products collected prior to the study for other protocols may be used as part of the backup. Patients who are apheresed at the NIH may be apheresed on
  • another protocol.
  • -For apheresis, pediatric patients:
  • Must weigh at least 15 kg body weight;
  • Preserved renal function (creatinine <=2.5 mg/dL; <=3+ proteinuria); preserved hepatic function (bilirubin <=2.0 mg/dl);
  • -Must be negative for co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive) or hepatitis C virus (HCV ribonucleic acid (RNA) positive), adenovirus, parvovirus B 19 or toxoplasmosis or mycobacterial infection (prior or current).
  • -For females of reproductive potential, must agree to use of 2 highly effective contraception throughout study participation and for at least 3 months after the study.
  • For females:
  • Condoms, male or female, with or without a spermicide;
  • Diaphragm or cervical cap with spermicide;
  • Intrauterine device;
  • Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA- approved contraceptive method;
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
  • Agreement to adhere to Lifestyle Considerations throughout study duration.
  • Ability of subject (Patient/Legal Guardian) to understand and the willingness to sign a written informed consent document.
  • For the Natural History Protocol (05-I-0213): All patients must be willing to allow storage of blood samples for future studies.
  • Must provide a durable power of attorney (DPA) for health care decisions to an appropriate adult relative or guardian in accordance to NIH-200 "NIH Advance Directive for Health Care and Medical Research Participation."

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • -Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements.
  • Contraindication for leukapheresis (anemia Hb <8 g/dl, cardiovascular instability, severe coagulopathy).
  • Patients who are unable to lie prone during the bone marrow harvesting procedure (in the case of bone marrow harvest, contraindication to general anesthesia).
  • Have a 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated adult donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure.
  • Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies.
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  • Altered organ function as outlined below observed within 8 weeks of entering this trial.
  • Hematologic
  • Anemia (hemoglobin < 8 g/dl).
  • Neutropenia (absolute granulocyte count <1,000/mm3 ).
  • Thrombocytopenia (platelet count < 150,000/mm3).
  • Prothrombin Time (PT) INR or Partial thromboplastin time (PTT) > 2 X the upper limits of normal (ULN) (patients with a correctable deficiency controlled on medication will not be excluded).
  • Cytogenetic abnormalities known to be associated with hematopoietic defect on peripheral blood or bone marrow.
  • Infectious
  • Evidence of infection with HIV-1 and -2, Hepatitis B, Hepatitis C, adenovirus, parvovirus B 19 or toxoplasmosis within 8 weeks prior to mobilization/apheresis or bone marrow harvest. Cytomegalovirus (CMV) infection is allowable as long as the infection is under control.
  • History of infection with mycobacteria or Bacille Calmette-Guerin (BCG) vaccination.
  • Pulmonary
  • Resting O2 saturation by pulse oximetry < 90% on room air.
  • Cardiac
  • Abnormal electrocardiogram (ECG) indicating cardiac pathology.
  • Uncorrected congenital cardiac malformation with clinical symptomatology.
  • Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension.
  • Poor cardiac function as evidenced by LV ejection fraction <40% on echocardiogram.
  • Neurological
  • Significant neurologic abnormality by examination.
  • Uncontrolled seizure disorder.
  • Renal
  • Renal insufficiency: serum creatinine >=2.5 mg/dl, or >=3+ proteinuria.
  • Chemistry Lab abnormalities: Serum sodium >= 156 mmol/L or <= 129 mmol/L, potassium >= 6.1 mmol/L or <= 2.9 mmol/L, calcium >= 3.2 mmol/L or < 1.74 mmol/L , magnesium >= 1.24 mmol/L or < 0.39 mmol/L, phosphate >= 5.1 mmol/L or < 1.9 mmol/L.
  • Serum transaminases > 5X the upper limit of normal (ULN).
  • Serum bilirubin > 2X the upper limit of normal (ULN).
  • Serum glucose > 1.5X the upper limit of normal (ULN).
  • General
  • Expected survival < 6 months.
  • Major congenital anomaly.
  • Known allergic reactions to components of busulfan or dimethyl sulfoxide (DMSO) or contraindication for administration of conditioning medication.
  • Evidence of active malignant disease.
  • Treatment with another investigational drug or other intervention within 6 months.
  • Unable to undergo apheresis as per the NIH CC Department of Transfusion Medicine Standard of Care apheresis procedures.
  • Patients who are hemodynamically unstable (systolic or diastolic blood pressure fall of 20 mm Hg from the stable patient's baseline measurement) or requiring mechanical respiratory assistance are excluded.
  • History of vasculitis.
  • Administration of gamma-interferon within 21 days before the infusion of transduced, autologous CD34+ cells.
  • Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Part B- Phase I/II, Non-Randomized, Single Site Study, Open-label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease

Background:

X-Linked Chronic Granulomatous Disease (X-CGD) is caused by a gene mutation that makes the immune system to not work properly. Researchers want to see if a lentiviral gene transfer treatment will have the ability to make the patient s immune system more normal, in particular reduce the risk of CGD related infections. The gene transfer takes a person s own stem cells, cultures them to put the normal gene in, then gives the cells back to the person.

Read more

Objective:

To test a gene transfer treatment for X-CGD.

Eligibility:

Participants aged 3-60 with X-CGD

Design:

Participants will be screened under protocol 05-I-0123. They will undergo:

Medical history

Physical exam

Heart tests

Imaging tests, as needed

Blood tests

Lung function tests, as needed

Dental and audiology exams, if needed

Quality of life questionnaire

Bone marrow aspiration. A needle will be inserted into the hip bone or breastbone to collect bone marrow.

Some screening tests will be repeated during the study.

Participants will have an apheresis procedure under protocol 94-I-0073. Stem cells will be collected.

Participants will get a series of drugs to prepare them for the gene transfer.

Participants will stay at the NIH Clinical Center for a little over a month. They will get a central line. It is a large intravenous (IV) catheter that is placed into a vein of the neck, chest, or arm. They will get chemotherapy and their corrected stem cells through their IV line.

Participants will have 12 follow-up outpatient visits in the 2 years after their gene transfer, as well as visits with their local doctor. Then they will enroll in another study for long-term follow-up visits that will last for 13 years.

Read the detailed description

Study Description:

This is a Phase I/II, non-Randomized, Single site study, open-label study of a single infusion of autologous CD34+ cells transduced ex vivo with pCCLChimGp91/VSVg lentiviral vector in 10 patients with X-Linked CGD.

Objectives:

Primary Objective:

To evaluate the safety, efficacy and stability by biochemical and functional reconstitution in progeny of engrafted cells at 12 months Secondary Objectives:

Endpoints:

  • Clinical efficacy and longitudinal evaluation of clinical effect in terms of augmented immunity against bacterial and fungal infection
  • Determine the number of days of antibiotic usage before compared to after gene therapy
  • Transduction efficiency of CD34+ hematopoietic cells from XCGD patients by ex vivo lentivirus-mediated gene transfer
  • Evaluation of engraftment kinetics and stability

Primary Endpoint:

  1. The primary safety objective of this procedure will be assessed by recording the incidence of adverse events.
  2. Record clinical adverse events and clinically significant laboratory abnormalities.
  3. Evaluate overall incidence of adverse events for the study as a whole.
  4. Monitor the incidence of serious adverse events.
  5. The primary efficacy objective of this study will be determined by measuring the percentage of subjects who have >= 10% oxidase positive granulocytes by dihydrorhodamine (DHR) flow cytometry at month 6 and 12 after transplant.

Secondary Endpoints:

  1. Assess immunological reconstitution: Restoration of neutrophil oxidase function (> 10%) as measured by DHR flow cytometry (clinical), and/or cytochrome C (O2 production, research), at 24 months. The % DHR + neutrophils will be measured at week 4, 5, 6, 7, 8, 10, 12 and month 6, 9, 12, 18 and 24.
  2. Assess hematopoietic stem cell (HSC) transduction and engraftment:
  3. Determine the percentage of transduced CD34+ hematopoietic cells infused.
  4. Measure the average vector copy number (VCN) in mature blood cells (at week 4, 6, 7, 8, 10, 12 and month 6, 9, 12, 18 and 24) by quantitative polymerase chain reaction (qPCR) or droplet digital polymerase chain reaction (ddPCR).
  5. Assess health by:
  6. The nutritional status (height, weight, serum albumin) at 24 months
  7. Growth and development of pediatric subjects at 24 months
  8. Frequency of severe infections or other health issues, including inflammatory complications (requiring intravenous [IV] antibiotics and/or hospitalization for treatment)
  9. Measurement of inflammatory markers at 1, 2, 3, 6, 9, 12, 18, and 24 months, compared to baseline
  10. Colitis assessment based on CDAI (Crohn s Disease Activity Index) and fecal calprotectin at 6, 12, and 24 months, compared to baseline
  11. Quality of Life (QOL) questionnaire (baseline, 6, 12 and 24 months)

Exploratory Endpoints:

  1. Evaluation of the human microbiome during XCGD gene therapy
  2. Evaluation of inflammatory cytokines and antibody development to Gp91, etc
Being tested
Busulfan, Tocilizumab, Eltrombopag, Sirolimus, pCCLChimGp91lentiviral vector containing the human gp91 phox (CYBB) gene
Keywords
Gene Therapy, UCLA, CGD
Medical subject headings
Granulomatous Disease, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    Conditioning drug

  • TocilizumabDrug

    Monoclonal Antibody

  • EltrombopagDrug

    Thrombopoietin Receptor Agonist

  • SirolimusDrug

    Post transplant immunosuppressant drug

  • pCCLChimGp91lentiviral vector containing the human gp91 phox (CYBB) geneOther

    Intervention Infusion on Day 0

Study groups in NCT07113743
Study groupRoleWhat they receive
X-linked CGDExperimentalNon-randomized single arm
Receives: Drug: Busulfan; Drug: Tocilizumab; Drug: Eltrombopag; Drug: Sirolimus; Other: pCCLChimGp91lentiviral vector containing the human gp91 phox (CYBB) gene

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety

    1. The primary safety objective of this procedure will be assessed by recording the incidence of adverse events. a) Record clinical adverse events and clinically significant laboratory abnormalities. b) Evaluate overall incidence of adverse events for the study as a whole. c) Monitor the incidence of serious adverse events.

    Measured: Throughout the study

  2. Efficacy

    The primary efficacy objective of this study will be determined by measuring the percentage of subjects who have >= 10% oxidase positive granulocytes by DHR flow cytometry at month 6 and 12 after transplant.

    Measured: 6 months and 1 year

Secondary outcomes (3)

  1. Assess immunological reconstitution

    Restoration of neutrophil oxidase function (> 10%) as measured by DHR flow cytometry (clinical), and/or cytochrome C (O2 production, research), at 24 months. The % DHR + neutrophils will be measured at week 4, 5, 6, 7, 8, 10, 12 and months 6, 9, 12, 18 and 24 months.

    Measured: Week 4, 5, 6, 7, 8, 10, 12 and months 6, 9, 12, 18 and 24 months.

  2. Assess HSC transduction and engraftment

    1. Determine the percentage of transduced CD34+ hematopoietic cells infused. b) Measure the average vector copy number (VCN) in mature blood cells (at week 4, 6, 7, 8, 10, 12 and month 6, 9, 12, 18 and 24) by qPCR or ddPCR.

    Measured: Week 4, 6, 7, 8, 10, 12 and month 6, 9, 12, 18 and 24)

  3. Assess health by

    1. The nutritional status (height, weight, serum albumin) at 24 months b) Growth and development of pediatric subjects at 24 months c) Frequency of severe infections or other health issues, including inflammatory complications (requiring IV antibiotics and/or hospitalization for treatment) d) Measurement of inflammatory markers at 1, 2, 3, 6, 9, 12, 18, and 24 months, compared to baseline e) Colitis assessment based on CDAI (Crohn s Disease Activity Index) and fecal calprotectin at 6, 12, and 24 months, compared to baseline f) Quality of life questionnaire (baseline, 6, 12 and 24 months).

    Measured: 1, 2, 3, 6, 9, 12, 18, and 24 months, compared to baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2025
  2. Study start10 Sep 2025
  3. Primary completion1 Sep 2028 (estimated)
  4. Study completion1 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07113743
Sponsor's protocol ID
10000186
Other IDs
000186-I
Status last verified
12 Aug 2026
First submitted
8 Aug 2025
Last updated
8 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Busulfan, Tocilizumab and Eltrombopag in people with Chronic Granulomatous Disease (CGD), run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (time frame: Throughout the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07113743.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.

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